Neither medication nor psychotherapy is effective in improving the prognosis for youngsters considered to be at high risk of developing psychosis, according to a major study just published.

The idea of identifying and treating young people at risk of becoming psychotic – because of a family history of schizophrenia, or because they’re showing some mild symptoms – has become very fashionable lately. But can we really do anything to pre-empt the disorder?

In this trial, 115 “ultra-high risk” Australian subjects were randomized to three different treatment conditions, or if they didn’t agree to treatment, they were just followed up to see what happened.

This shows all four of the subject groups did pretty much the same in terms of their likelihood of becoming psychotic. Neither cognitive therapy, nor the antipsychotic drug risperidone (at a low dose) had any effect: those given ‘supportive therapy’ (basically: sympathetic chats) and a placebo pill did just as well.

There probably wasn’t even a placebo effect: none of the three treatment groups did better than people who got no treatment at all (monitoring group), although people weren’t randomly assigned to that group, so that’s a little less clear.

Is this a surprise? Yes, if you believed the early studies to examine this question which claimed great things for drugs and therapy. But the current findings are no shock if you’ve been following the (much larger) recent trials – for example the British one from earlier in the year, which found zero benefit of cognitive therapy.

Early small trials have a nasty habit of not working out in the long run.

The other lesson here is that even “ultra-high risk” folks usually don’t get psychotic: only about 10-20% of them, in fact, became ill in the first two years of this study; the British results I mentioned are very similar.

So is this really “ultra high”? Relatively, yes it is; even a 10% risk is far higher than the chance that a random person on the street would have. But in absolute terms, perhaps not.

A concern here is that rounding these folks up, labelling and ‘treating’ them might make their lives worse, or even increase the risk of psychosis. That’s not just my opinion: that’s what the very cognitive therapists who eagerly run these trials believe (or ought to, if they’re being consistent with their own theories).

One of the key ideas in cognitive accounts of psychosis is that the belief and fear that one is ‘going crazy’, or that you’re otherwise abnormal, is itself a major source of stress that actually leads to worsening of symptoms.

What could be scarier than being told you’re at “ultra high risk”?

Preventing psychosis is a great idea in theory. But most bad ideas are.

I'm glad you're blogging about this research, but I think you're perhaps missing the full story, about intervention studies more broadly, and the UHR approach full stop.

[disclaimer – if it wasn't obvious – I work in this field and have a long collaboration with the authors of this study]

I was working in Melbourne during the recruitment period for this study, and I suspect that the low overall transition rate has a lot to do with the process of enrolling people into this clinical trial. I seem to remember it being a real slog, with the definite possibility that the slow recruitment resulted in people being less at risk than otherwise might be the case. Transition rates more generally have been dropping, for reasons that are still very unclear.

With respect to intervention studies – this one is negative, for sure. But this one is positive. Twice the numbers, for what that's worth. NNT of 9. Importantly, the study was embedded within an enrichment pathway, which may be key to preventing recruitment of people who meet risk criteria but for whom psychotic symptoms are not the main reason for help-seeking.

Which leads me to another point – that these young people are all help-seeking. No-one (to my knowledge) is suggesting going out into the general population, screening for psychosis risk, and intervening on that basis. The false positive rate would be huge – the whole point is indicated prevention. The people presenting to these UHR clinics are frequently very concerned about becoming psychotic (especially those who have family members with the disorder), so they already 'fear that they're going crazy' as you put it. Clinicians at UHR clinics are at least able to provide more evidence-based advice on the likelihood of such an outcome, and some intervention to reduce stress, substance use, and other potential triggers for a psychotic episode.

But the part of your post that annoyed me was your throwaway last line (which isn't even a very good one – really, most bad ideas are good in theory? Presumably most good ideas are also good in theory). Clearly you think that preventing psychosis is a 'bad idea' but I'm not sure what you base this on. Would you elaborate?

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

Hi Stephen, thanks very much for the comments.

Re: the recruitment, I can well believe that recruitment of not-very-unwell people contributed to the results, but I'd say that was a) a point against the (current) UHR criteria, which, that implies, are too broad and b) a worrying sign in the future, because historically in psychiatry, interventions have always expanded their remit over time and I can't see this being different.

I do see the point that maybe intervention would be helpful for the 'really' prodromal cases, quite possibly, that's what I meant about it being a good idea in theory – I wasn't being sarcastic. If it helps, it's good. But if, in practice, the great majority of people meeting criteria & getting these interventions aren't benefiting from it… then the theoretical benefits are not realized.

As for the fact that they're help-seeking. Well, maybe in this trial, but in the British one, 45 people were referred to the trial and declined because they didn't want help. So that is not universal.

And again, I really worry that in the future, if this becomes an accepted practice, people are going to get encouraged to seek help at the slightest sign of trouble.

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

P.S. Having said that, it is a bit unfair to criticize a treatment on the grounds that it might be overused in the future; I read somewhere that back in the 50s some psychiatrists opposed lithium for bipolar, because they feared it would end up also being used in unipolar depression… which is clearly silly (and didn't happen, lithium is very rarely used in depression.)

But I don't think what I'm saying is quite as silly because we're talking about a diagnose here really (“UHR”) and over the past 30 years so many psychiatric diagnoses have expanded that it's become the norm. ADHD, autism, bipolar are doing this as we speak (and schizophrenia with the “SCZ spectrum”), in the 90s it was depression…

http://www.blogger.com/profile/06845842769360018122 L. Paul Strait

This is a little surprising, and I'd like to examine what the inclusion criteria were. There have been several clinics working on early interventions in psychosis over the last 15 years and they have fairly consistently found that about 30% of untreated high risk individuals develop frank psychosis within 2 years, and that number drops to less than 10% with either low dose antipsychotics (generally either risperidone or olanzapine), high dose omega 3 fatty acids (something in the neighborhood of 3 grams a day of a combination of EPA and DHA), or cognitive therapy.

Interestingly, the 'false positive' rate tends to increase over time in every one of these clinics (generally I think because as they become well known they get more limit cases referred). I have 'false positive' in scare quotes because they are only false positives if you think you are diagnosing the prodromal phase of schizophrenia. If you are diagnosing a risk syndrome, the people who don't become psychotic still may have accurately been at risk.

Even the individuals who don't develop frank psychosis do develop other serious mental illnesses — affective disorders, schizotypal personality disorder, etc., so even in those cases I think the fact that they have contact with a mental healthcare provider is positive.

My initial response to reading about this study was disappointment that the treatment was ineffective. On the other hand though, I am relieved that that there is now no justification for giving antipsychotic drugs to people who might develop psychosis. Even though Risperidone is one of the newer “atypical” drugs, it can have unpleasant side-effects and potentially adverse health effects. I also find it encouraging to read about a study with no significant results being published, especially after there has been so much discussion recently about publication bias.

Overtreatment is indeed a major problem as well. While antipsychotics might be helpful (there are twotrials that are positive, for example), the cost-benefit ratio may well be unfavourable. A parallel can be drawn with mastectomy for breast cancer – it can be said to 'work' for early stage cancers, but it is now regarded as unnecessary because less radical interventions are as effective. I've made this argument in detail elsewhere.

Finally, who should get intervention? Bear in mind that the kinds of interventions proposed to prevent psychosis overlap considerably with the kind of clinical care offered for the presenting problems (with the obvious exception of antipsychotics, which I agree should not be used). Therefore, provided we require people to have a clear need-for-care, there are probably few ethical reasons to deny people these kinds of treatments. Furthermore, even though the majority of the UHR group do not become psychotic, their outcomes tend to be poor. So while preventing psychosis might not be a good idea, perhaps preventing 'bad outcomes' would be?

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

Scott McGreal: Yes, kudos to the authors for publishing, especially since the study got industry funding (from the makers of risperidone).

Just a small point about the authors publishing a negative study. In fact, the vast majority of RCTs looking at interventions to “prevent transition to psychosis” are negative in outcome.

The Omega study is a spectacular outlier in this regard. The recent Dutch study mentioned above (van der Gaag et al) was significant but not for the Intention to Treat analysis. The recent study by Morrison and colleagues using CBT was also negative and flawed (http://keithsneuroblog.blogspot.co.uk/2012/04/cbt-you-spin-me-round.html)Add negative outcomes for McGlashan et al 2006; McGorry et al., 2002 and Phillips et al., 2007; Morrison et al., 2004; Morrison et al., 2007

And finally none of the studies following up at 24 and 36 months find a difference in transitions.So not sure if too much kudos to be accredited – as almost all are negative – kind of suggesting some likely problem with 'the enterprise'

http://www.blogger.com/profile/16938658278079810327 jamzo

keep in mind that the ultra high risk for psychosis initiative is based on the assumption that a crisis of psychosis can be prevented

and they are testing antipsychotic drugs and/or therapy as the means to do this

maybe cancer, strokes, heart attacks, and other health crises can be prevented via similar means

Anonymous

There is an intervention that has significant evidentiary support — raising the offspring of mothers with schizophrenia in healthy adoptive homes:

Why would anything mainstream psychiatry do “prevent” the extreme states of mind, breakdowns and problems in living that get labeled “psychosis”?

Psychiatry's entire interpretive system and conceptual framework is nothing but an invalid medicalization of human distress.

Therefore it should never surprise that these quacks can't “prevent” anything.

I'm very lucky to have escaped psychiatry at great personal cost, and I'm very happy to have had the opportunity, too often robbed from young people, to find alternatives and to thoroughly understand the dangerous quackery that psychiatry is.

To label someone “unwell” just because they experience crises and come to cleave to “bizarre” beliefs, and to have so many people literally believing they are literally dealing with a bona fide “medical disease”, has got to be the most destructive idea humanity has ever come up with in relation to “helping” people through the problems of the human experience.

Having mastered my mind and my thoughts in spite of psychiatric quackery and violent human rights abusing interventions, my task is always to stay under the radar and ensure these brain rapists don't get their hands on my thinking organ ever again.

Labeling someone “psychotic” or “schizophrenic” or whatever quack name calling psychiatry invents next, is not helping somebody. It is mystifying personal problems, and holding innocent people hostage in psychiatry's quest to be seen as real doctors, which they are most decidedly not.

No worthless quack who flushed his medical degree down the toilet by becoming a psychiatrist, has any insight into why I underwent periods of overwhelming crisis and troubling thoughts.

I'm a very lucky to have been able to have escaped psychiatry. So many people linger and die stuck forever in an endless cycle of quackery and lies.

Brandy Nolan

As a parent of a child who has early onset childhood schizophrenia, I can truly say that therapy and meds do help! My child has been Halluinations & delutions since age two, now age 12. Her father has the disorder and many other of his family members…they tend to to get help and they live a life of horror, whereas my child is living as normal as a life as she can due to the help I get her.

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

Ah, “problems in living”, brilliant stuff.

Since all human problems are “problems in living” – no-one has any trouble dying or staying dead – we can shorten that to just “problems” and, bingo, it turns out that psychiatry is all rubbish, because in fact, people with problems just have “problems”!

Mind you, you only spent a hundred words or so saying that; Szasz wrote whole books on that tautology.

No – and I said as much in my original post with my point about labelling experiences & hence making things worse.

So I've been down the path of that argument, I've gone as far as is wise to go. I also know that if you go much further than I did you end up in error.

Anonymous

“Since all human problems are 'problems in living' – no-one has any trouble dying or staying dead – we can shorten that to just 'problems' and, bingo, it turns out that psychiatry is all rubbish, because in fact, people with problems just have 'problems'!”

Note the ever so predictable use of the word “just”, as in “just problems”. Problems can be severe, dramatic, terrible, horrible, and extreme, but they are still problems.

I think the reason the “brain disease” fanatics hate the word problem, is because it doesn't soud science-ey enough for them.

You can rubbish Szasz's carefully prosecuted more than half century exposition of psychiatry's error all you like.

I'm a person who has experienced the often severe personal problems that get labeled “schizophrenia”, I don't take psychiatric drugs, and no physician ever examined my brain and proved it diseased, nor did they for any other person who got the same label.

But by all means, continue to believe the severity of bizarreness of a train of thought proves the person's brain is diseased.

And indoctrinating scared young people to believe they are passive victims of an active brain disease, which is what psychiatry in the context of this blog post is, IS rubbish.

And catastrophically harmful rubbish at that.

I reiterate, I could not be more thankful that I escaped the cult of psychiatry scientism.

And it's not just rhetoric that enabled Szasz to connect with people who have actually experienced and beat these problems, there's other things too, like the fact psychiatry started the 20th century with nothing but a book of quack nosology holding it up, and here we are in the 21st century and again, nothing but a book of quack nosology holding it up.

Critics of psychiatry don't deny the severity of the problematic situations, behaviors and thought that can arise in a human lifetime, we just don't see any compelling reason to take the leap of faith required to agree that psychiatry has “proven” that these problems are brain diseases.

There tends to be a divide between people who spend their lives imbibing journal articles, and the common folkk who can see the obvious. The quack sitting behind a desk that doesn't even pick a up a single piece of medical equipment, has slapped a label on you, he hasn't diagnosed a brain disease.

But I can see how total 24/7 immersion in the slowly built up creation story that plays out in the go nowhere conceptually flawed “research” could indoctrinate a fellow.

Me? I'm just lucky to have escaped this menace.

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

“Note the ever so predictable use of the word “just”, as in “just problems”. Problems can be severe, dramatic, terrible, horrible, and extreme, but they are still problems.”

Read what I wrote – I said you're the one saying they are just/only/nothing but/etc. problems. Which is a diagnosis – you (and Szasz) are in the business of handing out psychiatric diagnoses no less than anyone else. Yours are just rather simpler.

“There tends to be a divide between people who spend their lives imbibing journal articles, and the common folkk who can see the obvious.”

Maybe so, but I think you don't like me because I'm someone who both knows the science and has personal experience on the receiving end of psychiatry – and still disagrees with you.

I'm the Black Swan that shouldn't exist.

Anonymous

“Maybe so, but I think you don't like me because I'm someone who both knows the science and has personal experience on the receiving end of psychiatry – and still disagrees with you.

I'm the Black Swan that shouldn't exist.”

So if you sit on the opposite of a desk of a quack who declares you “clinically depressed brain diseased” yet performs no test, and you “know the science” (read: imbibes journal articles), that makes you a “black swan”? I don't think so, there are multitudes like you, that's how the Ponzi scheme keeps itself going.

And believe me, “on the receiving end” of psychiatry, as in voluntarily swallowing SSRI's doesn't even begin to become close to knowing the receiving end. And you know it. So don't even start, Mr. “I don't believe in scientism”.

Wrong. I'm not in the business of “handing out psychiatric diagnoses”….

Get this, when we don't consider human problems MEDICAL problems, the word “diagnosis” doesn't apply. Simple. But hard to get your head around after years of indoctrination I know, hence the hostility from you.

When someone felt sad and got the “depression label” and bought the lie that their brain was diseased, they really ain't no “skeptic”.

http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

You seem to have a “problem in leaving” silly comments – that's my diagnosis.

And you'd be just as “scientific” as any “diagnosis” you yourself have received.

You're no skeptic, that's for sure!

http://www.blogger.com/profile/00187465138890222167 LokaSamasta

Hey I managed to get psychosis unexpectedly, because of stress, and I survived without drugs* or psychiatrists and I really enjoyed it and now I'm fine.

*apart from hashish, but that doesn't count.

Anonymous

An angle that I feel failed to be explored were the devastating side effects and risks of antipsychotics (well-documented, not controversial). Seeing the impact on patients, it is frequently hard to justify administration even if it did help with psychosis. The fact that it may not makes the risk:reward ratio entirely unjustifiable to the point of horrific. Otherwise, great article. Thanks!

as far as mental health/psychiatry–are suggesting 50% of us might have a mental illness at some point in our lives– which ive been very concerned about– challenging–because i dont like misery or miserisers– ive realised its actuallyt 100%— we are all in “mad pain” mad land— in our own way anyway– at varying degrees of “comfort” -or “discomfort” at sometimes / many times–even everyday of our lives—if we want to be honest about it— some of us get caught up too much and a bit lost in it all— some of us manage to find a reason,a way to back off within our psyche and keep/or get ourselves back on track—and safe for the moment–hopefully leadinbg to always– but for those who havent yet learnt that recipe, matured enough, arent worldly enough- and have taken mind bending drugs with their immaturity of mind and life- and in the majority of those/these afflicetd– suffered a drug immature induced psychosis—which is as real as a real non drug affflicted psychosis– psychosis is what psychosis does– that they get tagged and adversely drugged– when they should be shown a recipe and a way out of their temporary condition– guided,loved,helped.ie- cbt–they arent mad permanently- in need of lifelong shut them down psychotropics–and how dare anyone “misery” say they are, and on top of that misery– then to assure that misery assesment is correct– poison them with drugs thast have any mental iullness known to man in them– just to be sure to be sure–

its just getting lost/caught up in the mind–for most—9/10-stuck in the/a wandering mind—its only when we stand by/back superior moded and point and punish with”F#$%@d if i know poisons” that misery–arrogance and professionalism gets a guernsey– takes a fee/vegetates/destroys another life–and is the reason that those of us in the know come to these places in frustration and despair after thew damage is done/still being done—to try not only to save their own loved ones tortured adversely by psychiatry/mental health by growling at the drug dealling industry of psychiatry and mental health–but to try and save those vulnerable members of society potentially lining up to be labeled and brutalised by psychiatry /mental health and their majic pills– put in a box–like the song “we all go to university” or and we all take majic pills handed to us by those vested in “misery”-wearing strings.Anything in a white coat “government”–banks vested in drug companies and dollars– drug companies vested in banks and dollars –and the puppets themnselves the psychiatrists– and their puppets, the whitre coat believing sheople people. Us.Dont let anyone label your madness– its as valid and as necessary as the next blokes– you just need ythe tools to quieten it ,learn and understand the peace thats just like the madness– in each and everyone of us– and how to get it, the maturity to understand and cope better, a healthy body and habit to help yoiurself overcome, and a good non misery seeing-acting counsellor/guider to help you along and out of the temporary darkness that can become more permanent or burdensome if not helped with or if left alone, or if glossed over /deadened by a poison that retards.remember healthy body-healthy mind.

it works on scramble— jumble-scramble-ramble–too much emotion–too much thinking– too much rambling— easy to go on the ride–especially with mind altering drugs— hard to get off sometimes—but you can. dont let anyone tell you differently— you wont do it drinking misery in a bottle– you wont do it retarding yourself with mind altering substances– but you will do it if you reject misery and insanity– help yourself and get some help– two helps are nearly always better than one help– unless its a misery pushing drugs because theyre simply not good enough to impart words and wisdom that embolden or hearten —ease the pain– show the way.

Some of us are in the future of care— thats why what psychiatry is saying now, i and many others have said for twety years–words can heal– apparently their evolving–it was always just a majic pill– the only reason their changing their tune is because theyve been wrong for so long and society has evolved past and around them– common sense, loving care– has just started to leave them behing as they run for cover– “theyve been found out”. this so called relapse/their dressed up wisdom and their white coats is what theyre killing everyone with– relapse into what /towards your “original” “drug induced” insanity– is now apparently a “real psychosis” for “some reason” now—when did that real psychosis happen? — when the misery failed to see what was real and what wasnt–when the misery forecfull added his or her own insanity in a pill– or is it “really” a “neuroleptic withdrawal psychosis” otherwise known as a “supersensitivity psychosis” that they “psychiatrists” themselves admit happens going on or coming off psychotropics– or is it a convenient tag to keep the prisoners prisoners– to keep the egos and pockets full, of/for those vested in the majic of themselves, and their majic pills.

The only thing they wont admit is the insanity of/from caused by the pill being on the pill– which mind you they will admit have from 1500 reported and known adverse side effects to 2000 plus– adverse side effects in each and every psychotropic— reflecting/causing any mental illness known to man—yet they still point their bone at their victims– or should i say power point– Hello!– anybody home– yoo hoo– how can anyone call anyone anything whilst they have them on poisons with up to 2000 mental illness side effects in them.. Answer that? You cant! no one can– not honestly they cant.So what is it? fight fire with fire— since when did fighting fire with fire work— might in burning off season– but a mind body and soul insnt a forest is it— at some stage you will need water— the pill isnt the water– the pill is just another fire—a burning off/management pill– not a put the fire out pill— that comes with maturity and wisdom– knowledge–information–guidance–proper care—but ultimately the answers are in you— you just need to find them– maturity and knowledge– information–are the the things you need to find the answers you need— when i say you that means 80 to 90% of us– 80 to 90% of us all have the same or similar mental problems– just in varying degrees— we are all the same –except for the obvious 10% who more than nlikely need long term if not lifetime medication— shut them down medication because vnothing will– theyre the truly mad— the rest of us just think we are or have trouble with our thoughts /–madness– thaT I SAY WEVCE ALL GOT–its not exclusive to a special club– or a special people or person — its all of us —no need to make it special for only special people to know and treat— its more normalk than special– when you make it special you build it up— when thats very handy for the psychiatrist and his/her bag of majic pills– but when you down play it— make it par for all the course of life– it becomes something we all share and something we can all help each other cope/dealwith– its not specialised and dolled out to professionals to mysify us with and adversely drug us for.its something thast society in general needs to take account of/for–to stand up and be noticed for your peace of mind and your wisdom—sharing your peace– offering it up for others to see and be strengthened by– be shown the/a way by which to cope—find comfort in–a way out of trouble– not a way into trouble–like psychiatry has us doing– filling the community/society with sick– sad,miserasble trapped peoplke— we owe it to our families– our chilkdren– ourselves and each other to reject mental illness– start there– dont start accepting it– start not eccepting it– and go from there– if you start by accepting it–temporary and real forever/like psychiatry does–(although now that theyve been seen for their evil ways//theyve put two bob on temporary–just in case) where do you think you will end up–misery land thets where— if you start in temporary going away— youll stand every chance of it going away—thats common sense and hopefull and right– dont be fooled by drug dealers and miseries. If you want to be managed or manage misery— your immature- a fool or a drug company,-psychiatrist-mental health worker,your a loser. no one.—if you want to cure misery– your someone, your a winner.

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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.